Platelet malondialdehyde production and aggregation responses induced by arachidonate, prostaglandin-G2, collagen, and epinephrine in 12 patients with storage pool deficiency.
We assessed the integrity of the prostaglandin synthetic pathway by measuring malondialdehyde (MDA) production and studied platelet aggregation responses to arachidonic acid and PGG2 in 12 patients with storage pool deficiency (SPD). Eight patients were deficient only in dense granules (delta-SPD) and four were deficient in both dense and alpha-granules (alpha delta-SPD). Production of MDA in response to arachidonic acid (AA), epinephrine, and collagen suggested that the transformation of AA to prostaglandin metabolites was normal in delta-SPD but abnormal in alpha delta-SPD and that the liberation of AA from phospholipids were abnormal in the majority of patients with SPD. Since the content of secretable adenosine diphosphate (ADP) is diminished in SPD platelets, the aggregation responses of these platelets to AA and PGG2 were studied to help answer the question whether these agents aggregate platelets directly or through release of endogenous ADP. Among patients with delta-SPD, aggregation by both AA and PGG2 was decreased in four albinos whose platelets were markedly deficient in ADP. In contrast, normal, or less strikingly abnormal, responses were observed in patients whose platelets either contained higher levels of platelet ADP or showed increased sensitivity to ADP. The more marked impaired responses to AA and PGG2 in patients with alpha delta-SPD suggest that substances derived from alpha-granules may also play a role in platelet aggregation by these agents. The aggregation responses in these patients with various types of SPD is consistent with a theory that granule-derived ADP mediates platelet aggregation by AA and PGG2.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D003594:Cytoplasmic Granules; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008314:Malonates / Q000096:biosynthesis*; D008315:Malondialdehyde / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects*; D011462:Prostaglandins G / Q000494:pharmacology
D001095:Arachidonic Acids; D008314:Malonates; D011462:Prostaglandins G; D016718:Arachidonic Acid; D008315:Malondialdehyde; D003094:Collagen; D004837:Epinephrine